Medical devices having antimicrobial coatings thereon

ABSTRACT

The present invention provides a medical device, preferably a contact lens, which comprises an antimicrobial coating including at least one layer of polyquat of formula (I) or (II). The antimicrobial coating on the medical device of the invention has a high antimicrobial efficacy against microorganisms including Gram-positive and Gram-negative bacterial, a low toxicity, low coefficient of friction, and increased hydrophilicity while maintaining the desired bulk properties such as oxygen permeability and ion permeability of lens material. Such lenses are useful as extended-wear contact lenses. In addition, the invention provides a method for making a medical device, preferably a contact lens, having an antimicrobial coating thereon.

[0001] This application claims the benefit under 35 U.S.C. §119(e) ofUnited state provisional application Serial No. 60/332,289 filed Nov.14, 2001.

[0002] The present invention generally relates to a medical devicehaving an antimicrobial coating thereon. In particular, the presentinvention relates to an ophthalmic lens having an antimicrobial coatingthat has antimicrobial efficacy and low cytotoxicity as well as otherdesired properties such as low coefficient of friction, hydrophilicity,and high oxygen permeability and ion permeability. In addition, thisinvention provides a method for making a medical device having anantimicrobial coating.

BACKGROUND

[0003] Contact lenses are often exposed to one or more microorganismsduring wear, storage and handling. They can provide surfaces onto whichthe microorganisms can adhere and then proliferate to form a colony.Microbial adherence to and colonization of contact lenses may enablemicroorganisms to proliferate and to be retained at the ocular surfacefor prolonged periods and thereby may cause infection or otherdeleterious effects on the ocular health of the eye in which the lens isused. Therefore, it is desirous to make various efforts to minimizeand/or eliminate the potential for microorganism adhesion to andcolonization of contact lenses.

[0004] Many attempts have been made to develop antimicrobial medicaldevices. Two approaches have been proposed. One approach is toincorporate antimicrobial compounds into a polymeric composition formolding a contact lens. For example, Chalkley et al. in Am. J.Ophthalmology 1966, 61:866-869, disclosed that germicidal agents wereincorporated into contact lenses. U.S. Pat. No. 4,472,327 discloses thatantimicrobial agents may be added to the monomer before polymerizationand locked into the polymeric structure of the lens. U.S. Pat. Nos.5,358,688 and 5,536,861 disclose that contact lenses havingantimicrobial properties may be made from quaternary ammonium groupcontaining organosilicone polymers. European patent applicationEP0604369 discloses that deposit-resistant contact lenses can beprepared from hydrophilic copolymers that are based on 2-hydroxyethylmethacrylate and comonomers containing a quaternary ammonium moiety.Another example is an ocular lens material, disclosed in European patentapplication EP0947856A2, which comprises a quaternary phosphoniumgroup-containing polymer. A further example is U.S. Pat. No. 5,515,117which discloses contact lenses and contact lens cases made frommaterials which comprise polymeric materials and effective antimicrobialcomponents. There are some disadvantages associated with this approachfor making antimicrobial contact lenses. First, polymeric compositionshaving antimicrobial properties may not possess all properties desiredfor contact lenses, especially extended-wear contact lenses, whichhinders their practice uses. Second, antimicrobial compounds may exhibitgreatly diminished activity since they may not in contact withmicroorganisms adhered to the surface of contact lens.

[0005] The other approach for making antimicrobial medical devices is toform antimicrobial coatings, containing leachable or covalently attachedantimicrobial agents, on medical devices. Antimicrobial coatingscontaining leachable antimicrobial agents may not be able to provideantimicrobial activity over the period of time when used in the area ofthe human body. In contrast, antimicrobial coating containing covalentlybound antimicrobial agents can provide antimicrobial activity over arelatively longer period of time. However, antimicrobial compounds insuch coatings may exhibit greatly diminished activity when comparing theactivity of the unbound corresponding antimicrobial compounds insolution, unless assisted by hydrolytic breakdown of either the boundantimicrobial compounds or the coating itself.

[0006] Currently, a wide variety of antimicrobial agents have beenproposed to be used as coatings for contact lenses (see, for example,U.S. Pat. No. 5,328,954,). Prior known antimicrobial coatings includeantibiotics, lactoferrin, metal chelating agents, substituted andunsubstituted polyhydric phenols, amino phenols, alcohols, acid andamine derivatives, and quaternary ammonium group-containing compounds.However, such antimicrobial coatings have disadvantages and areunsatisfactory. The overuse of antibiotics can lead to proliferation ofantibiotic-resistant microorganisms. Other coatings may not have broadspectrum antimicrobial activity, may produce ocular toxicity or allergicreactions, or may adversely affect lens properties required for ensuringcorneal health and for providing the patient with good vision andcomfort.

[0007] Therefore, there is a need for antimicrobial coatings that canprovide high bactericidal efficacy and broad spectrum antimicrobialactivity coupled with low cytotoxicity. There is also a need for newcontact lenses having antimicrobial coatings, which have highbactericidal efficacy, a broad spectrum of antimicrobial activities, andminimal adverse effects on the wearer's ocular health and comfort. Suchcontact lenses may have increased safety as extended-wear contact lenseswhich could provide comfort, convenience, and safety.

[0008] One object of the invention is to provide an antimicrobialcoating which has a high antimicrobial efficacy coupled with lowcytotoxicity.

[0009] Another object of the invention is to provide a medical devicehaving an antimicrobial coating that has a high antimicrobial efficacycoupled with low cytotoxicity.

[0010] A further object of the invention is to provide a cost-effectiveand efficient process for forming an antimicrobial coating on a medicaldevice.

SUMMARY OF THE INVENTION

[0011] These and other objects of the invention are met by the variousaspects of the invention described herein.

[0012] The invention, in one aspect, provides a medical device having anantimicrobial surface coating and the following surface properties: alow coefficient of friction characterized by having an averaged value ofless than 1.4 and a hydrophilicity characterized by having an averagedcontact angle of less than 80 degree. The antimicrobial coatingpreferably comprises at least one layer of polymeric quaternary ammoniumgroup-containing compound (polyquats) and has a balance of highantimicrobial efficacy and low cytotoxicity.

[0013] The invention, in another aspect, provides a method for formingan antimicrobial coating on a medical device. The method comprisesapplying at least one layer of polymeric quaternary ammoniumgroup-containing compound on a medical device.

[0014] These and other aspects of the invention will become apparentfrom the following description of the presently preferred embodiments.The detailed description is merely illustrative of the invention anddoes not limit the scope of the invention, which is defined by theappended claims and equivalents thereof. As would be obvious to oneskilled in the art, many variations and modifications of the inventionmay be effected without departing from the spirit and scope of the novelconcepts of the disclosure.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Unless defined otherwise, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this invention belongs. Generally, thenomenclature used herein and the laboratory procedures are well knownand commonly employed in the art. Conventional methods are used forthese procedures, such as those provided in the art and various generalreferences. Where a term is provided in the singular, the inventors alsocontemplate the plural of that term. The nomenclature used herein andthe laboratory procedures described below are those well known andcommonly employed in the art. As employed throughout the disclosure, thefollowing terms, unless otherwise indicated, shall be understood to havethe following meanings.

[0016] An “article” refers to an ophthalmic lens, a mold for making anophthalmic lens, or a medical device other than ophthalmic lens.

[0017] A “medical device”, as used herein, refers to a device havingsurfaces that contact tissue, blood, or other bodily fluids of patientsin the course of their operation or utility. Exemplary medical devicesinclude: (1) extracorporeal devices for use in surgery such as bloodoxygenators, blood pumps, blood sensors, tubing used to carry blood andthe like which contact blood which is then returned to the patient; (2)prostheses implanted in a human or animal body such as vascular grafts,stents, pacemaker leads, heart valves, and the like that are implantedin blood vessels or in the heart; (3) devices for temporaryintravascular use such as catheters, guide wires, and the like which areplaced into blood vessels or the heart for purposes of monitoring orrepair; and (4) ophthalmic lenses. In a preferred embodiment, medicaldevices are ophthalmic lenses.

[0018] An “ophthalmic lens”, as used herein, refers to any lens intendedfor use in intimate contact with the eye of the user. This includes,without limitation, intraocular lenses, ocular implants, hard contactlenses, soft contact lenses, and corneal onlays.

[0019] The “outer surface” of a lens, as used herein, refers to thesurface of the lens which faces away from the eye during wear. The outersurface, which is typically substantially convex, may also be referredto as the front curve of the lens. The “inner surface” of a lens, asused herein, refers to the surface of the lens which faces towards theeye during wear. The inner surface, which is typically substantiallyconcave, may also be referred to as the base curve of the lens.

[0020] “Ophthalmically compatible”, as used herein, refers to a materialor surface of a material which may be in intimate contact with theocular environment for an extended period of time without significantlydamaging the ocular environment and without significant user discomfort.Thus, an ophthalmically compatible contact lens will not producesignificant corneal swelling, will adequately move on the eye withblinking to promote adequate tear exchange, will not have substantialamounts of protein or lipid adsorption, and will not cause substantialwearer discomfort during the prescribed period of wear.

[0021] “Ocular environment”, as used herein, refers to ocular fluids(e.g., tear fluid) and ocular tissue (e.g., the cornea) which may comeinto intimate contact with a contact lens used for vision correction,drug delivery, wound healing, eye color modification, or otherophthalmic applications.

[0022] A “monomer” means a low molecular weight compound that can bepolymerized. Low molecular weight typically means average molecularweights less than 700 Daltons.

[0023] A “macromer” refers to medium and high molecular weight compoundsor polymers that contain functional groups capable of furtherpolymerization. Medium and high molecular weight typically means averagemolecular weights greater than 700 Daltons.

[0024] “Polymer” means a material formed by polymerizing one or moremonomers.

[0025] “Surface modification”, as used herein, refers to treating anarticle to alter its surface properties. For example, the surfacemodification of a contact lens includes, without limitation, thegrafting of monomers or macromers onto polymers to make the lensbiocompatible, deposit resistant, more hydrophilic, more hydrophobic, orthe deposing of polyionic materials (LbL coating) to increase the lenshydrophilic properties or to impart antimicrobial or antifungalproperties.

[0026] “LbL coating”, as used herein, refers to a coating which isobtained by layer-by-layer (“LbL”) deposition of polyelectrolytes on anarticle. The LbL coating of an article is not covalently attached to thesurface of the article. Any suitable LbL polyelectrolyte depositiontechniques can be used in the LbL coating. For example, a pending U.S.patent application Ser. No. 09/199,609, filed on Nov. 25, 1998,discloses an LbL polyelectrolyte deposition technique that involvesconsecutively dipping a substrate into oppositely charged polyionicmaterials until a coating of a desired thickness is formed.

[0027] As used herein, “asymmetrical coatings” on an ophthalmic lensrefers to the different coatings on the first surface and the oppositesecond surface of the ophthalmic lens. As used herein, “differentcoatings” refers to two coatings that have different surface propertiesor functionalities.

[0028] A “capping layer”, as used herein, refers to the last layer of acoating material which is applied onto the surface of a medical device.

[0029] A “polyquat”, as used herein, refers to a polymeric quaternaryammonium group-containing compound.

[0030] As used herein, a “polyionic material” refers to a polymericmaterial that has a plurality of charged groups, such aspolyelectrolytes, p- and n-type doped conducting polymers. Polyionicmaterials include both polycationic (having positive charges) andpolyanionic (having negative charges) materials.

[0031] An “antimicrobial coating”, as used herein, refers to a coatingthat impart to a medical device the ability to decrease or eliminate orinhibit the growth of microorganisms on the surface of the medicaldevice.

[0032] An “antimicrobial agent”, as used herein, refers to a chemicalthat is capable of decreasing or eliminating or inhibiting the growth ofmicroorganisms such as that term is known in the art.

[0033] The “oxygen transmissibility” of a lens, as used herein, is therate at which oxygen will pass through a specific ophthalmic lens.Oxygen transmissibility, Dk/t, is conventionally expressed in units ofbarrers/mm, where t is the average thickness of the material [in unitsof mm] over the area being measured and “barrer/mm” is defined as:

[(cm ³ oxygen)/(cm ²)(sec)(mm ² Hg)]×10⁻⁹

[0034] The “oxygen permeability”, Dk, of a lens material does not dependon lens thickness. Oxygen permeability is the rate at which oxygen willpass through a material. Oxygen permeability is conventionally expressedin units of barrers, where “barrer” is defined as:

[(cm ³ oxygen)(mm)/(cm ²)(sec)(mm ² Hg)]×10⁻¹⁰

[0035] These are the units commonly used in the art. Thus, in order tobe consistent with the use in the art, the unit “barrer” will have themeanings as defined above. For example, a lens having a Dk of 90 barrers(“oxygen permeability barrers”) and a thickness of 90 microns (0.090 mm)would have a Dk/t of 100 barrers/mm (oxygen transmissibilitybarrers/mm).

[0036] The “ion permeability” through a lens correlates with both thelonoflux Diffusion Coefficient and the lonoton Ion PermeabilityCoefficient.

[0037] The lonoflux Diffusion Coefficient, D, is determined by applyingFick's law as follows:

D=−n′/(A×dc/dx)

[0038] where

[0039] n′=rate of ion transport [mol/min]

[0040] A=area of lens exposed [mm²]

[0041] D=lonoflux Diffusion Coefficient[mm²/min]

[0042] dc=concentration difference [mol/L]

[0043] dx=thickness of lens [mm]

[0044] The lonoton Ion Permeability Coefficient, P, is then determinedin accordance with the following equation:

ln(1−2C(t)/C(0))=−2APt/Vd

[0045] where:

[0046] C(t)=concentration of sodium ions at time t in the receiving cell

[0047] C(0)=initial concentration of sodium ions in donor cell

[0048] A=membrane area, i.e., lens area exposed to cells

[0049] V=volume of cell compartment (3.0 ml)

[0050] d=average lens thickness in the area exposed

[0051] P=permeability coefficient

[0052] An lonoflux Diffusion Coefficient, D, of greater than about0.2×10⁻³ mm²/min is preferred, while greater than about 0.64×10⁻³mm²/min is more preferred and greater than about 1.0×10⁻³ mm²/min ismost preferred.

[0053] An “averaged value of coefficient of friction” refers to a valueof coefficient of friction, which is obtained by averaging measurementsof at least 3 individual medical devices.

[0054] An “averaged contact angle” refers to a contact angle (SessileDrop), which is obtained by averaging measurements of at least 3individual medical devices.

[0055] In general, the present invention is directed to a medical devicehaving a core material and an antimicrobial surface coating (hereinafterantimicrobial coating) formed thereon and the following surfaceproperties: a low coefficient of friction characterized by having anaveraged value of less than 1.4 and a hydrophilicity characterized byhaving an averaged contact angle of less than 80 degree. Theantimicrobial coating can comprise any known suitable antimicrobialagents. Exemplary antimicrobial agents include, without limitation,antibiotics, lactoferrin, metal chelating agents, substituted andunsubstituted polyhydric phenols, amino phenols, alcohols, acid andamine derivatives, and quaternary ammonium group-containing compounds.Antimicrobial agents in the antimicrobial coating of a medical devicecan be covalent bound to or entrapped to the medical device.

[0056] In particular, the present invention is directed to a medicaldevice, preferably an ophthalmic lens, more preferably a contact lens,having an antimicrobial coating comprising at least one layer,preferably one capping layer, of polymeric quaternary ammonium saltcompounds or the like. Surprisingly, it has been discovered that apreviously known polymeric quaternary ammonium salt compound (polyquat)of formula (I) or (II)

[0057] can be used to form on a contact lens an antimicrobial coatinghaving a high antimicrobial efficacy and low cytotoxicity. Especially,when such antimicrobial coating is formed on a contact lens which ismade from ophthalmically compatible materials, for example, materialsdisclosed in U.S. Pat. No. 5,849,811, it provides high antimicrobialactivity coupled with low cytotoxicity, increases surfacehydrophilicity, decreases coefficient of friction, and has a minimaladverse effects on the desirable bulk properties of the lens, such asoxygen permeability, ion permeability, and optical properties.Coefficient of friction may be one of important parameters that mayaffect the on-eye movement and thereby the wearer's comfort. Highcoefficient of friction may increase the likelihood of damagingmechanically the ocular epithelia and/or may lead to ocular discomfort.An antimicrobial coating of the present invention may find particularuse in extended-wear contact lenses.

[0058] In formula (I), R₁, R₂, R₃ and R₄ are identical or different fromone another. They are C₁-C₁₀ hydrocarbon radicals, preferably C₁ to C₆alkyl radicals or C₁ to C₆ alkyl radicals having one or more hydroxylgroups, more preferably methyl, ethyl, or benzyl radicals, even morepreferably methyl radicals.

[0059] In formula (I), A and B are identical or different from oneanother. They are n-alkylene groups having 3 to 15 carbon atoms orn-alkylene groups having 3 to 15 carbon atoms and one or more hydroxylgroups. Preferably, either one of A and B is hexamethylene radical(—CH₂CH₂CH₂CH₂CH₂CH₂—). More preferably, either one of A and B ishexamethylene radical (—CH₂CH₂CH₂CH₂CH₂CH₂—) and the respective otherone is an n-alkylene group having 6 to 10 carbon atoms. Even morepreferably, either one of A and B is hexamethylene radical(—CH₂CH₂CH₂CH₂CH₂CH₂—) and the respective other one is an n-alkylenegroup having 8 to 10 carbon atoms.

[0060] Where either one of A and B is hexamethylene radical(—CH₂CH₂CH₂CH₂CH₂CH₂—) and the respective other one is an n-alkyleneradical having 6 to 12 carbon atoms, the polyquat of formula (I) will berepresented by PQ6−x, in which x represents the number of carbon atomsof n-alkylene radical.

[0061] It is possible as well to provide the polymer chains with varyingproportions of alkylene groups of different lengths. For example, one ofA and B may be hexamethylene radical (—CH₂CH₂CH₂CH₂CH₂CH₂—), while therespective other one is n-alkylene radical having 6, 8, 10, or 12 carbonatoms, and these being present in different proportions. It is possible,for example, to produce polymers which contain 80% of hexamethyleneunits and 10% each of decamethylene and dodecamethylene groups.Depending on the starting material used, these different alkylene groupsmay be distributed statistically or in a more or less orderly fashionthroughout the polymer chain.

[0062] In formula (I), the index y characterizes the chain length of thepolymer of formula (I) and is a number from about 10 to 500, preferablya number from 25 to 400, and more preferably a number from 50 to 300. Xis chlorine, bromine, or iodine.

[0063] In formula (II), X is chlorine, bromine, or iodine. The index ncharacterizes the chain length of the polymer of formula (II) and is anumber from about 100 to 5000, preferably a number from 500 to 4000, andmore preferably a number from 500 to 3000. R₅ and R₆ are identical ordifferent from one another. They are n-alkyl groups having 1 to 10carbon atoms or n-alkyl groups having 1 to 10 carbon atoms and one ormore hydroxyl groups. Preferably, R₅ and R₆ are identical and methylgroups.

[0064] Methods for making a polymer of formula (I) are well known in theart. Reference is made in this context to U.S. Pat. Nos. 2,261,002,2,271,378 and 3,898,188. Generally, a polymer of formula (I) can besynthesized by reacting a diamine having of formula (III)

[0065] with a dihalide of formula XBX, in which R₁, R₂, R₃, R₄, A, B,and X are as defined above.

[0066] It has also been discovered that an unleachable antimicrobialcoating can be formed on a medical device made from a core material bycovalently attaching at least one layer of polymers of polyquat offormula (I) to the surface of the medical device or by non-covalentlyapplying at least one layer of polyquat of formula (I) onto the surfaceof the medical device using a layer-by-layer polyelectrolyte depositiontechnique. The antimicrobial activity of the polyquat of formula (I) isnot diminished significantly in the antimicrobial coating formed on themedical device.

[0067] In a preferred embodiment, a medical device of the inventioncomprises a core material and an antimicrobial LbL coating including atleast one polyquat-polyanionic bilayer which is composed of one layer ofa polyanionic material and one layer of polyquat of formula (I) or (II).In a more preferred embodiment, the medical device of the inventionfurther comprises a plurality of polyelectrolyte bilayers. Apolyelectrolyte bilayer is composed of a first layer of a firstpolyionic material and a second layer of a second polyionic materialhaving charges opposite of the charges of the first polyionic material.

[0068] A polycationic material used in the present invention cangenerally include any material known in the art to have a plurality ofpositively charged groups along a polymer chain. For instance, suitableexamples of such polycationic materials can include, but are not limitedto, poly(allylamine hydrochloride) (PAH), poly(ethyleneimine) (PEI),poly(vinylbenzyltriamethylamine) (PVBT), polyaniline (PAN or PANI)(p-type doped) [or sulphonated polyaniline], polypyrrole (PPY) (p-typeddoped), and poly(pyridinium acetylene).

[0069] A polyanionic material used in the present invention cangenerally include any material known in the art to have a plurality ofnegatively charged groups along a polymer chain. For example, suitablepolyanionic materials can include, but are not limited to,polymethacrylic acid (PMA), polyacrylic acid (PAA),poly(thiophene-3-acetic acid) (PTAA), poly(4-styrenesulfonic acid)(PSS), sodium poly(styrene sulfonate) (SPS) and poly(sodium styrenesulfonate) (PSSS).

[0070] The foregoing lists are intended to be exemplary, but clearly arenot exhaustive. A person skilled in the art, given the disclosure andteaching herein, would be able to select a number of other usefulpolyionic materials.

[0071] In order to alter various characteristics of the coating, such asthickness, the molecular weight of the polyionic materials includingpolyquats can be varied. In particular, as the molecular weight isincreased, the coating thickness generally increases. However, if theincrease in molecular weight increase is too substantial, the difficultyin handling may also increase. As such, polyionic materials used in aprocess of the present invention will typically have a molecular weightM_(n) of about 2,000 to about 150,000. In some embodiments, themolecular weight is about 5,000 to about 100,000, and in otherembodiments, from about 75,000 to about 100,000.

[0072] In another preferred embodiment, a medical device of theinvention comprises a core material and an antimicrobial LbL coatingincluding a capping layer of polyquat of formula (I) or (II). With suchcapping layer of polyquat of formula (I) or (II), an antimicrobialcoating on a medical device of the invention can provide a directcontact with the antimicrobial agents, polyquat of formula (I) or (II)for microorganisms and thereby have a higher antimicrobial efficacy.

[0073] In another preferred embodiment, a medical device of theinvention comprises a core material and an antimicrobial LbL coatingincluding a plurality of layers of polyquat of formula (I) or (II). Suchantimicrobial coating may provide higher concentration of antimicrobialagents and thereby increase antimicrobial efficacy.

[0074] In accordance with the present invention, the core material of amedical device may be any of a wide variety of polymeric materials.Exemplary core materials include, but are not limited to, hydrogels,silicone-containing hydrogels, polymers and copolymers of styrene andsubstituted styrenes, ethylene, propylene, acrylates and methacrylates,N-vinyl lactams, acrylamides and methacrylamides, acrylonitrile, acrylicand methacrylic acids. A preferred group of polymeric materials formingophthalmic lenses are those materials which are highly oxygen permeable,such as fluorine- or siloxane-containing polymers. In particular, thepolymeric materials described in U.S. Pat. No. 5,760,100 are anexemplary group, and the teachings of this patent are incorporatedherein by reference.

[0075] One embodiment of the invention is a method for producing amedical device having a core material and an antimicrobial coatingincluding a capping layer of polyquats of formula (I) or (II),comprising covalently coupling the polyquats of formula (I) or (II) tothe core material.

[0076] Any known suitable method for covalent coupling of polyquats tothe core material can be used. For example, a contact lens made from ahydrogel, such as lotrafilcon A, lotrafilcon B, or balafilcon, is dippedinto or sprayed with a solution containing a diaziridine compound, whichis subsequently attached covalently to the surface of the contact lensvia a thermal process, so as to functionalize the contact lens. Suchfunctionalized lenses can be placed in a container containing a polyquatsolution and then irradiated with blue light for 30 minutes so thatpolyquats are covalently attached to the functionalized lens.

[0077] It should be understood that the surface of the medical devicecan be chemically modified before covalently coupling polyquats to themedical device or a different material can be first grafted onto orbound to the core material and then covalently coupled with polyquats.

[0078] Another embodiment of the invention is a method for producing amedical device having a core material and an antimicrobial LbL coatingincluding a capping layer of polyquats of formula (I) or (II) comprisingapplying the antimicrobial LbL coating onto the core material using alayer-by-layer polyelectrolyte deposition technique.

[0079] It has been discovered and disclosed in U.S. application Ser. No.09/005,317 that complex and time-consuming pretreatment of a corematerial (medical device) is not required prior to non-covalentlybinding of a polyionic material to the core material. By simplycontacting a core material of a medical device, for example, a contactlens, with one or more solutions each containing one or more polyionicmaterials, an LbL coating can be formed on a medical device to modifythe surface properties of the core material of the medical device. AnLbL coating can be a single layer or a bilayer or multiple bilayers.

[0080] Application of an LbL coating may be accomplished in a number ofways as described in pending U.S. patent application (application Ser.Nos. 09/005,317, 09/774,942, 09/775,104), herein incorporated byreference in their entireties. One coating process embodiment involvessolely dip-coating and dip-rinsing steps. Another coating processembodiment involves solely spray-coating and spray-rinsing steps.However, a number of alternatives involve various combinations of spray-and dip-coating and rinsing steps may be designed by a person havingordinary skill in the art.

[0081] One dip-coating alternative involves the steps of applying acoating of a first polyionic material to a core material of a medicaldevice by immersing said medical device in a first solution of a firstpolyionic material; rinsing the medical device by immersing the medicaldevice in a rinsing solution; and, optionally, drying the medicaldevice. This procedure can be repeated using a second polyionicmaterial, with the second polyionic material having charges opposite ofthe charges of the first polyionic material, in order to form apolyionic bilayer. This bilayer formation process may be repeated aplurality of times in order to produce a thicker LbL coating. Apreferred number of bilayers is about 5 to about 20 bilayers. While morethan 20 bilayers are possible, it has been found that delamination mayoccur in some LbL coatings having an excessive number of bilayers.

[0082] The immersion time for each of the coating and rinsing steps mayvary depending on a number of factors. Preferably, immersion of the corematerial into the polyionic solution occurs over a period of about 1 to30 minutes, more preferably about 2 to 20 minutes, and most preferablyabout 1 to 5 minutes. Rinsing may be accomplished in one step, but aplurality of rinsing steps can be quite efficient.

[0083] Another embodiment of the coating process is a single dip-coatingprocess as described in U.S. application Ser. No. 09 775104, hereinincorporated by reference in its entirety. Such single dip-coatingprocess involves dipping a core material of a medical device in asolution containing a negatively charged polyionic material and apositively charged polyionic material in an amount such that the molarcharge ratio of said solution is from about 3:1 to about 100:1. Multiplebilayers can be formed on a medical device by using this singledip-coating process.

[0084] Another embodiment of the coating process involves a series ofspray coating techniques. The process generally includes the steps ofapplying a coating of a first polyionic material to a core material of amedical device with a first solution of a first polyionic material;rinsing the medical device by spraying the medical device with a rinsingsolution; and optionally, drying the medical device. Similar to thedip-coating process, the spray-coating process may be repeated with asecond polyionic material, with the second polyionic material havingcharges opposite of the charges of the first polyionic material.

[0085] The contacting of the medical device with solution, eitherpolyionic material or rinsing solution, may occur by a variety ofmethods. For example, the medical device may be dipped into bothsolutions. One preferred alternative is to apply the solutions in aspray or mist form. Of course, various combinations may be envisioned,e.g., dipping the medical device in the polyionic material followed byspraying the rinsing solution.

[0086] The spray coating application may be accomplished via a number ofmethods. For example, a conventional spray coating arrangement may beused, i.e., the liquid material is sprayed by application of fluid,which may or may not be at elevated pressure, through a reduced diameternozzle which is directed towards the deposition target.

[0087] Preferably, a spraying process is selected from the groupconsisting of an air-assisted atomization and dispensing process, anultrasonic-assisted atomization and dispensing process, a piezoelectricassisted atomization and dispensing process, an electro-mechanical jetprinting process, a piezo-electric jet printing process, apiezo-electric with hydrostatic pressure jet printing process, and athermal jet printing process; and a computer system capable ofcontrolling the positioning of the dispensing head of the sprayingdevice on the ophthalmic lens and dispensing the coating liquid. Thosespraying coating processes are described in U.S. Application No.60/312,199, herein incorporated by reference in its entirety. By usingsuch spraying coating processes, an asymmetrical coating can be appliedto a medical device. For example, the back surface of a contact lens canbe coated with a hydrophilic and/or lubricous coating material and thefront surface of the contact lens can be coated with an antimicrobialmaterial. It is also possible to produce a coating on a contact lens,the coating having a functional pattern so as to provide simultaneouslymultiple benefits to a wearer.

[0088] In accordance with the present invention, polyionic materialsolutions can be prepared in a variety of ways. In particular, apolyionic solution of the present invention can be formed by dissolvingthe polyionic material(s) in water or any other solvent capable ofdissolving the materials. When a solvent is used, any solvent that canallow the components within the solution to remain stable in water issuitable. For example, an alcohol-based solvent can be used. Suitablealcohols can include, but are not limited to, isopropyl alcohol,hexanol, ethanol, etc. It should be understood that other solventscommonly used in the art can also be suitably used in the presentinvention.

[0089] Whether dissolved in water or in a solvent, the concentration ofa polyionic material in a solution of the present invention cangenerally vary depending on the particular materials being utilized, thedesired coating thickness, and a number of other factors. However, itmay be typical to formulate a relatively dilute aqueous solution ofpolyionic material. For example, a polyionic material concentration canbe between about 0.001% to about 0.25% by weight, between about 0.005%to about 0.10% by weight, or between about 0.01% to about 0.05% byweight.

[0090] In general, the polyionic solutions mentioned above can beprepared by any method well known in the art for preparing solutions.For example, in one embodiment, a polyanionic solution can be preparedby dissolving a suitable amount of the polyanionic material, such aspolyacrylic acid having a molecular weight of about 90,000, in watersuch that a solution having a certain concentration is formed. In oneembodiment, the resulting solution is a 0.001 M PAA solution. Oncedissolved, the pH of the polyanionic solution can also be adjusted byadding a basic or acidic material. In the embodiment above, for example,a suitable amount of 1 N hydrochloric acid (HCl) can be added to adjustthe pH to 2.5.

[0091] Polycationic solutions can also be formed in a manner asdescribed above. For example, in one embodiment, poly(allylaminehydrochloride) having a molecular weight of about 50,000 to about 65,000can be dissolved in water to form a 0.001 M PAH solution. Thereafter,the pH can also be adjusted to 2.5 by adding a suitable amount ofhydrochloric acid.

[0092] In some embodiments of the present invention, it may be desirableto apply a solution containing both polyanionic and polycationicmaterials within a single solution. For example, a polyanionic solutioncan be formed as described above, and then mixed with a polycationicsolution that is also formed as described above. In one embodiment, thesolutions can then be mixed slowly to form the coating solution. Theamount of each solution applied to the mix depends on the molar chargeratio desired. For example, if a 10:1 (polyanion:polycation) solution isdesired, 1 part (by volume) of the PAH solution can be mixed into 10parts of the PAA solution. After mixing, the solution can also befiltered if desired.

[0093] A medical device of the invention can also be made by firstapplying an antimicrobial coating to a mold for making a medical deviceand then transfer-grafting the antimicrobial coating to the medicaldevice made from the mold, in substantial accordance with the teachingsof U.S. patent application (Ser. No. 09/774,942), herein incorporated byreference in its entirety.

[0094] Methods of forming mold sections for cast-molding a contact lensare generally well known to those of ordinary skill in the art. Theprocess of the present invention is not limited to any particular methodof forming a mold. In fact, any method of forming a mold can be used inthe present invention. However, for illustrative purposes, the followingdiscussion has been provided as one embodiment of forming a mold onwhich a color image can be printed in accordance with the presentinvention.

[0095] In general, a mold comprises at least two mold sections (orportions) or mold halves, i.e. first and second mold halves. The firstmold half defines a first optical surface and the second mold halfdefines a second optical surface. The first and second mold halves areconfigured to receive each other such that a contact lens forming cavityis formed between the first optical surface and the second opticalsurface. The first and second mold halves can be formed through varioustechniques, such as injection molding. These half sections can later bejoined together such that a contact lens-forming cavity is formedtherebetween. Thereafter, a contact lens can be formed within thecontact lens-forming cavity using various processing techniques, such asultraviolet curing.

[0096] Examples of suitable processes for forming the mold halves aredisclosed in U.S. Pat. No. 4,444,711 to Schad; U.S. Pat. No. 4,460,534to Boehm et al.; U.S. Pat. No. 5,843,346 to Morrill; and U.S. Pat. No.5,894,002 to Boneberger et al., which are also incorporated herein byreference.

[0097] Virtually all materials known in the art for making molds can beused to make molds for making contact lenses. For example, polymericmaterials, such as polyethylene, polypropylene, and PMMA can be used.Other materials that allow UV light transmission could be used, such as.quartz glass.

[0098] Once a mold is formed, a transferable antimicrobial LbL coating,which comprises at least one layer of polyquat of formula (I) or (II),can be applied onto the optical surface (inner surface) of one or bothmold portions by using the above-described LbL deposition techniques.The inner surface of a mold portion is the cavity-forming surface of themold and in direct contact with lens-forming material. A transferableantimicrobial LbL coating can be applied onto the mold portion definingthe posterior (concave) surface of a contact lens or on the mold sectiondefining the anterior surface of a contact lens or on both moldportions.

[0099] Once a transferable antimicrobial LbL coating is applied onto theoptical surface of one or both mold portions, a lens material can thenbe dispensed into the contact lens forming cavity defined by theassembled mold halves. In general, a lens material can be made from anypolymerizable composition. In particular, when forming a contact lens,the lens material may be an oxygen-permeable material, such as flourine-or siloxane-containing polymer. For example, some examples of suitablesubstrate materials include, but are not limited to, the polymericmaterials disclosed in U.S. Pat. No. 5,760,100 to Nicolson et al., whichis incorporated herein by reference. The lens material can then becured, i.e. polymerized, within the contact lens-forming cavity to formthe contact lens, whereby at least a portion of the transferable coatingdetaches from the optical surface and reattaches to the formed contactlens.

[0100] Thermal curing or photo curing methods can be used to curing apolymerizable composition in a mold to form an ophthalmic lens. Suchcuring methods are well-known to a person skilled in the art.

[0101] The previous disclosure will enable one having ordinary skill inthe art to practice the invention. In order to better enable the readerto understand specific embodiments and the advantages thereof, referenceto the following examples is suggested.

EXAMPLE 1 Preparation of Coating Solutions

[0102] Polyacrylic Acid (PAA) Solution

[0103] A solution of polyacrylic acid (PAA) having an averaged molecularweight of about 90,000 is prepared by dissolving a suitable amount ofPAA in water to have [PAA]=0.001 M. PAA concentration is calculatedbased on the repeating unit in PAA. Once dissolved, the pH of the PAAsolution is adjusted to a desired value.

[0104] Poly(Allylamine Hydrochloride) (PAH) Solution

[0105] A solution of poly(allylamine hydrochloride) (PAH) having anaveraged molecular weight of about 60,000 is prepared by dissolving asuitable amount of the material in water to form a 0.001 M PAH solution.PAH concentration is calculated based on the repeating unit in PAH. Oncedissolved, the pH of the PAH solution is adjusted to a desired value.

[0106] Polyquat (PQ) Solutions

[0107] A solution of polyquat (PQ6-6) of formula (I), in which R₁, R₂,R₃, and R₄ are methyl groups, and A and B are hexamethylene groups, isprepared by dissolving a suitable amount of PQ6-6 in water to have adesired PQ6-6 concentration. Once dissolved, the pH of the PQ6-6solution is adjusted to a desired value.

[0108] A solution of polyquat (PQ6-10) of formula (I), in which R₁, R₂,R₃, and R₄ are methyl radicals, and A and B are hexamethylene anddecamethylene groups respectively, is prepared by dissolving a suitableamount of PQ6-10 in water to have a desired PQ6-6 concentration. Oncedissolved, the pH of the PQ6-10 solution is adjusted to a desired value.

[0109] A solution of polyquat (PQ6-12) of formula (I), in which R₁, R₂,R₃, and R₄ are methyl groups, and A and B are hexamethylene anddodecamethylene respectively, is prepared by dissolving a suitableamount of PQ6-12 in water to have a desired PQ6-6 concentration. Oncedissolved, the pH of the PQ6-12 solution is adjusted to a desired value.

[0110] A solution of poly(diallyidimethylammonium chloride) (PDADMAC) isprepared by dissolving a suitable amount of PDADMAC in water to have adesired PDADMAC concentration. Once dissolved, the pH of the PDADMACsolution is adjusted to a desired value.

EXAMPLE 2 Preparation of Contact lenses Having LbL Coatings

[0111] This example illustrates LbL coatings and several types ofantimicrobial coatings which are formed on soft contact lenses made of afluorosiloxane hydrogel material, lotrafilcon A.

[0112] (1) Coating Comprising Four and Half Bilayers:

[0113] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA

[0114] The contact lenses are dipped in a PAA solution (0.001 M, pH 2.5)for 30 min, rinsed with ultra-pure water, then dipped in a PAH solution(0.001 M, pH 7.5) for 5 minutes, rinsed with ultra-pure water for 1minute. Three more bilayers are added by alternatively dipping in thesolutions of PAA (0.001 M, pH 3.5) and PAH (0.002M, pH 7.5), with arinse step in-between. The contact lenses with four bilayers ofpolyelectrolytes is dipped in the PAA solution (0.001 M, pH 3.5) andrinsed with ultra-pure water for 1 minute. The lenses are then packagedin saline and sterilized.

[0115] (2) Antimicrobial Coating Comprising 6 Bilayers:

[0116] PAA/PAH/PAA/PAH/PAA/PAH/PA/PAH/PAA/PAH/PAA/PQ6-12

[0117] The contact lenses are dipped in a PAA solution (0.001 M, pH 2.5)for 30 min, rinsed with ultra-pure water, then dipped in a PAH solution(0.001 M, pH 7.5) for 5 minutes, rinsed with ultra-pure water for 1minute. Four more bilayers are added by alternatively dipping in thesolutions of PAA (0.001 M, pH 3.5) and PAH (0.002M, pH 7.5), with arinse step in-between. The contact lenses with five bilayers ofpolyelectrolytes is dipped in the PAA solution (0.001 M, pH 3.5) andrinsed with ultra-pure water for 1 minute. Finally, a capping layer ofPQ6-12 is deposited by dipping lenses in a PQ6-12 solution (300 ppm, pH6.5). The lenses are then packaged in saline and sterilized.

[0118] (3) Antimicrobial Coating Comprising 5 Bilayers:

[0119] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-12

[0120] The contact lenses are dipped in a PAA solution (0.001 M, pH 2.5)for 30 minutes, dipped in a PAH solution (0.001 M, pH 4.5) for 5minutes, rinsed with ultra-pure water, dipped in the PAA solution for 5minutes, and rinsed with ultra-pure water. This procedure of dipping inan alternative fashion in the PAH and PAA solutions for 5 minutes andrinsing with water between two dipping steps is repeated until four andhalf bilayers with PAA as the outer layer are formed on the lenses. Thenthe lenses are dipped in a PQ6-12 solution (300 ppm, pH 5.1) for 5minutes, followed by a water rinsing step. The lenses are then packagedin saline and sterilized.

[0121] (4) Antimicrobial Coating Comprising 5 Bilayers:

[0122] PAA/PAH/PAA/PAH/PAA/PAH/PA/PAH/PAA/PQ6-10

[0123] The contact lenses are dipped in a PAA solution (0.001 M, pH 2.5)for 30 minutes, then dipped in a PAH solution (0.001 M, pH 4.5) for 5minutes, rinsed with ultra-pure water, then dipped in the PAA solutionfor 5 minutes, rinsed with ultra-pure water. This procedure of dippingin an alternative fashion in the PAH and PAA solutions for 5 minutes andrinsing with water between two dipping steps is repeated until four andhalf bilayers with PAA as the outer layer are formed on the lenses. Thenthe lenses are dipped in a PQ6-10 solution (300 ppm, pH 5.4) for 5minutes, followed by water rinsing step. The lenses are then packaged insaline and sterilized.

[0124] (5) Antimicrobial Coating Comprising 5 Bilayers:

[0125] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-6

[0126] The contact lenses are dipped in PAA (0.001 M, pH 2.5) for 30min, then dipped in PAH (0.001 M, pH 4.5) for 5 min, rinsed withultra-pure water, then dipped in PAA solution for 5 min, rinsed withultra-pure water. This procedure of dipping in an alternative fashion inthe PAH and PAA solutions for 5 minutes and rinsing with water betweentwo dipping steps is repeated until four and half bilayers with PAA asthe outer layer are formed on the lenses. Then the lenses are dipped ina PQ6-6 solution (300 ppm, pH 5.9) for 5 min, followed by water rinsingstep. The lenses are then packaged in saline and sterilized.

[0127] (6) Antimicrobial Coating Comprising 6 Bilayers:

[0128] PAA/PAH/PAA/PQ6-1 O/PAA/PQ6-10/PAA/PQ6-10/PAA/PQ6-1 O/PAA/PQ6-10

[0129] The contact lenses are dipped in a PAA solution (0.001 M, pH 2.5)for 30 minutes, then dipped in a PAH solution (0.001 M, pH 4.5) for 5min, and then rinsed with ultra-pure water. The lenses with the firstbilayer formed thereon are then dipped in the PAA solution for 5minutes, rinsed with ultra-pure water and then dipped in a PQ6-10solution (300 ppm, pH 5.4) for 5 minutes, rinsed with water, and thendipped in the PAA solution and rinsed with water. The procedurecomprising 5-minute dips in the PQ6-10 solution and in the PAA solutionand water rinse steps between two dipping steps is repeated until adesired number of bilayers with either PAA or PQ6-10 as the outer layerare achieved. The lenses are then packaged in saline and sterilized.

[0130] (7) Antimicrobial Coating Comprising 6 Bilayers:

[0131]PAA/PAH/PAA/PDADMAC/PAA/PDADMAC/PAA/PDADMAC/PAA/PDADMAC/PAA/PDADMAC

[0132] The contact lenses are first dipped in a PAA solution (0.001 M,pH 2.5) for 30 minutes, then dipped in a PDADMAC solution (0.001 M, pH3.5) for 5 minutes, rinsed with ultra-pure water for 1 minute, thendipped in a PAA solution (0.001 M, pH 4.4) for 5 minutes, rinsed withultra-pure water for 1 minute. This procedure of dipping in analternative fashion in the PDADMAC and PAA solutions for 5 minutes andrinsing with water between two dipping steps is repeated until a desirednumber (from 5 to 10) of bilayers with PDADMAC as the outer layer areformed on the lenses. The lenses are then packaged in saline andsterilized.

[0133] It has been found that the pH of the polyquat solution used inthe coating process can affect the quality of the antimicrobial coating,such as polyquat coverage. When the pH of the polyquat solution used inthe coating process is low (e.g., less than 2.5) or high (e.g., higherthan 7.0), delamination of the LbL coating can occur. Preferably, the pHof the polyquat solution used in the coating process is from about 3.0to about 7.0, in order to obtain an antimicrobial coating with goodpolyquat coverage. It has also been found that there is no need foradjusting the pH of the polyquat solution used in the coating process.The unadjusted pH of the polyquat solution (300 ppm) generally is fromabout 5.0 to about 6.0, which is within the preferred pH range.

EXAMPLE 3

[0134] This example illustrates how to produce a covalently-attachedantimicrobial coating on a contact lens made of lotrafilcon A,lotrafilcon B, or Balafilcon.

[0135] The contact lens is functionalized by spraying with or dippedinto a diaziridine compound and then covalently coupling the diaziridinecompound to the contact lens via a thermal process. Such functionalisedlens is placed in an open dish containing a polyquat (PQ6-6, PQ6-10,PQ6-12, or PDADMAC) solution of about 10 μg/ml and irradiated with bluelight for 30 minutes.

EXAMPLE 4

[0136] Coefficient of friction of a contact lens can be measured by asled-on-block type of friction tester as follow. Under a certain load(e.g., about 3 grams), a contact lens is slid back and forth, at aprescribed speed, against a biologically relevant substrate and both thenormal force (N) and the tangential force (F_(T)) are measured. Thecoefficient of friction of the contact lens is calculated based on theequation of μ=F_(T)/N.

[0137] A preferred friction tester comprises: a stationary lens holderassembly, a biologically relevant substrate, a horizontally movableplatform, and a plurality of force measuring means.

[0138] The stationary lens holder assembly preferably comprises an“A-shaped” holder bracket and a lens holder having a lens-supportingsurface. The lens supporting surface of the lens holder has a convexcurvature capable of accommodating the back (concave) surface of acontact lens. The lens holder is preferably held by a means in thecenter of the “A-shaped” holder bracket. The head end of the “A-shaped”stationary sample holder bracket is connected to a first force measuringmeans (e.g., a load cell from Transducer Techniques) by, for example, aKevlar® fiber. The two foot end of the “A-shaped” holder bracket areconnected to nylon string attached with two {fraction (1/2)}″ steelextension springs. The first force measuring means and the steelextension springs are mounted to the frame of the tester.

[0139] The horizontally movable platform can be, for example, a tableplatform (x-table) which moves uniaxially at various speeds andaccelerations. The x-table preferably has a dimension of 163 mm long and19.1 mm wide and can provide a test area having about 140 mm long andabout 14.7 mm wide. An example of the x-table is a Model 41 LinearPositioner which is powered by a ZETA Drive Compumotor (Parker HannifinCorporation), which operates unidirectional at maximum velocities of1800 mm/min and accelerations of 9000 mm/s².

[0140] The biologically relevant substrate can be any material andpreferably is a powder-free surgical glove with Biogel® Coating″ fromRegent®. Preferably, the finger of the glove is cut into a singlerectangular strip, and stretched and attached to the x-table by aphysical means, for example, jumbo paper clips. Before testing, thesubstrate attached onto the x-table is lubricated with two drops of adesired lubricant, for example, ultra pure water or Softwear® saline(CIBA vision). Any air between the substrate and the x-table should beremoved. The desired lubricant should be applied evenly on thesubstrate. The substrate should be even and consistent throughout.

[0141] Preferably, there are three force-measuring means, a first, asecond and a third force-measuring means. Any suitable knownforce-measuring means can be used. An example is a 100-gram load cellsfrom Transducer Techniques. The first force-measuring means is attachedto the sample holder to measure tangential forces (friction forces,F_(T)) in two opposite directions. The second and third force-measuringmeans reside under the x-table to measure normal forces (N) in thedownward direction. The other load cell Values outputted by the normalload cells are converted to grams by a Versatile Amplifier/Conditioner(Transducer Techniques).

[0142] Measurements of coefficient of friction is performed on thepreferred friction tester as follows. A contact lens is placed on a lensholder with the back surface of the contact lens against thelens-supporting surface of the lens hold. The lens holder with thecontact lens is assembled with the “A-shaped” holder bracket and thenplaced in contact with a desired lubricated substrate. This substrate ismounted to a horizontally movable table platform that is capable ofmoving uniaxially at various speeds and accelerations. About 3 grams ofweight is loaded onto the lens holder. This load may represent the forcepressed on a contact lens by a blink of eyelids. The treeforce-measuring means (3 Load cells from Transducer Techniques) measuresimultaneously the normal (N) and frictional (F_(T)) forces that areproduced from the interaction between the contact lens and the substratelubricated with a desired lubricant. Multiple data points are takenduring a measurement of coefficient of friction of a contact lens. Ateach data point, the coefficient of Friction μ, is calculated asfollows:

μ=F _(T) /N

[0143] in which F_(T) represent actual data reading at each pointobtained by the first force measuring means after correcting for thepreloading provided by the springs (tangential load cell) during slidingof the substrate against the contact lens and preferably has a unit ofgram; N is the sum of N₁ and N2; N1 represents actual data reading ateach point obtained by the second force-measuring means after correctingfor any preloading by the test assembly (normal load cell#1) duringsliding of substrate against the contact lens and preferably has a unitof gram; and N₂ represents actual data reading at each point obtained bythe third force-measuring means after correcting for any preloading bythe test assembly (normal load cell#2) during sliding of substrateagainst the contact lens and has preferably a unit of gram. The average(μ_(Ave)) of all μ's at every data point will be used to represent thevalue of coefficient of friction of a contact lens.

[0144] More preferably, the friction tester further comprises a computersystem that controls the tester, collects readings of the normal andtangential forces simultaneously as the biologically-relevant substrateinteracts with contact lens, calculates coefficient of friction, andrecords and charts the forces (F_(T) and N) and the coefficient offriction (μ) at each data point during testing.

EXAMPLE 5 Antimicrobial Activity of Contact Lenses Having One or MoreLayer of Polyquats

[0145] Contact lenses having an LbL coating ofPAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA (4½ bilayers) and a capped layer ofpolyquat are tested for antimicrobial activity against Pseudomonasaeruginosa #3, which is isolated from a corneal ulcer.

[0146] Effects of pH of polyquat coating solutions on antimicrobialactivity are studied. The contact lenses are prepared as described inExample 2. The pHs of the PQ6-12 solution used in forming the cappinglayer of polyquat are from 2.5 to 6.5. The contact lenses are incubatedfor three days with Pseudomonas aeruginosa GSU #3 suspended in PBS. Theinoculum size is 1.0×10⁴ cfu/ml. No significant difference inantimicrobial activity of contact lenses is observed for those solutionhaving a pH of from 3.0 to 6.5. For further antimicrobial activityassays, the pH of the polyquat solution is within 3.0 to 6.5.

[0147] The contact lenses are prepared as described in Example 2. ThepHs of the PQ6-12 solution used in forming the capping layer of polyquatare 5.5 and 6.5 respectively. The contact lenses are soaked in a cellsuspension of 1×10³ of Pseudomonas aeruginosa GSU #3 at 37° C. for 20hours. Lenses are removed from the cell suspension and immediatelysoaked/rinsed in 250 ml of PBS (Dulbecco). The rinsing step is repeatedfor 3 consecutive times. After rinsing with PBS, each lens is placed ona petri dish. Molten agar is poured into the petri dish containing onelens. The agar dish containing the lens is inverted and incubated atabout 30° C. to 35° C. for about 24 to 48 hours.

[0148] As a positive control, contact lenses with coatings, each havingfour and half bilayers PAA/PAH/PAA/PAH/PAA/PAH/PAA, are tested forantimicrobial activity against Pseudomonas aeruginosa GSU #3 accordingto the above-described procedures.

[0149] As a negative control, contact lenses with coatings, each havingfour and half bilayers PAA/PAH/PAA/PAH/PAA/PAH/PAA, are soaked in bleachfor 30 minutes and then rinsed with PBS. The lenses are then inoculatedwith Pseudomonas aeruginosa GSU #3 and antimicrobial activity is testedaccording to the above-described procedures.

[0150] Results of antimicrobial activity assays are shown in Table 1.TABLE 1 Colonies on the lenses No. 1 lens No. 2 lens No. 3 lens Lenscoated w/PQ6-12¹ 3 1 0 Lens coated w/PQ6-12² 0 2 2 Positive control++++* ++++* ++++* Negative control none none none

[0151] Surface antimicrobial activities of contact lenses withantimicrobial coating are also assayed. Contact lenses are prepared asdescribed in Example 2 and each contains an antimicrobial coating ofPAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA (4%2 bilayers) and a capped layer ofpolyquat (PQ6-6, PQ6-10, or PQ6-12). The pHs of the polyquat solutions(300 ppm) used in forming the capping layer of polyquat are unadjustedand from about 5.0 to about 6.0. Two types of control contact lenses areused. Each of the first type of control contact lenses comprises an LbLcoating having 4½ bilayers, PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA. Thesecond type of control contact lenses is plasma-coated contact lenses.The plasma-coated contact lenses are prepared in substantial accordancewith teachings in PCT Publication No. WO 96/31792 to Nicolson et al. Allcontact lenses are made of lotrafilcon A. 200 microliter of inoculumsolution (10⁴/CFU of Pseudomonas aeruginosa GSU #3) is placed on thetest lenses, incubated for ˜18 hours at 25° C. A portion of the inoculumis extracted, serially diluted and plated out on agar plates forcomparison to determine the microbial load of each lens type. At 24hours, colony counts are taken from each lens. Results are shown inTable 2. TABLE 2 cfu recovered from Contact lenses the surface of thelens* Control 1 (4½ bilayers) TNTC^(#) (solid lawn of bacteria) Control2 (plasma-coating) TNTC^(#) (solid lawn of bacteria) A capping LbL layerof PQ6-6 377 A capping LbL layer of PQ6-10  0 A capping LbL layer ofPQ6-12  0

[0152] Results in Table 2 indicate the antimicrobial activity on thesurface of the contact lenses having antimicrobial coatings. Theantimicrobial coatings with a capping layer of PQ6-12 or PQ6-10 showrelatively high antimicrobial efficacy. The antimicrobial coating with acapping layer of PQ6-6 shows antimicrobial activity but less than theactivity demonstrated by the other antimicrobial coatings containingPQ6-12 or PQ6-10.

[0153] Contact lenses having a coating comprising covalently attachedPQ6-12 are tested for antimicrobial activity against Staphylococcusaureus (ATCC 6538). The contact lenses are prepared as described inExample 3. Lenses to which polyquats are covalently attached are placedin 0.5 ml of 1×10⁴ cfu Staphylococcus aureus (ATCC 6538) in anartificial tear fluid at 37° C. with shaking for 24 hours. Thecomposition and preparation of the artificial tear fluid is described byMirejovsky et al. in Optom. Vis. Sci. 68: 858-864 (1991), hereinincorporated by reference. After 24 hours, the contact lenses areremoved and rinsed 3 times in 250 ml of phosphate buffered saline (PBS)and then placed in a vial containing 10 ml of Dulbecco's PBS, sonicatedfor 6 minutes followed by vortexing for 1-2 minutes. The effluent fromeach lens is serially diluted, plated out and incubated inverted at 35°C. Colonies are counted after about 24 to 48 hours of incubation. As acontrol, contact lenses made of the same material (lotrafilcon A) arefunctionalized with a diaziridine compound. These control contact lensesare also tested using the identical antimicrobial activity assayprocedure. Number of cfu recovered from the control contact lenses isabout 1.9×10⁴. Number of cfu recovered from the contact lenses having acoating comprising covalently attached PQ6-12 is undetectable.

EXAMPLE 6 Surface Properties of Contact Lenses Having AntimicrobialCoatings

[0154] The contact angle generally measures the surface hydrophilicityof a contact lens. In particular, a low contact angle corresponds tomore hydrophilic surface. Average contact angles (Sessile Drop) ofcontact lenses are measured using a VCA 2500 XE contact anglemeasurement device from AST, Inc., located in Boston, Mass. The averagedcontact angle of a contact lens, which is made of lotrafilcon A andwithout any coating (LbL or plasma), is about 112 degree. When suchcontact lens has a surface modification through LbL coating or plasmacoating, the averaged contact angle is decreased generally to less than70 degrees. Where a contact lens having an antimicrobial coatingcomprising one or more layer of polyquat, the averaged contact angle isdetermined to be from about 30 degree to about 65 degrees.

[0155] Coefficient of friction (COF) may be one of parameters thatmeasure the easiness of the on-eye movement of a contact lens. Highcoefficient of friction may increase the likelihood of damagingmechanically the ocular epithelia. The COF is measured as described inExample 4. Multiple lenses are measured to obtain the averaged COF. Acontact lens without any surface modification (i.e., plasma treatment orLbL coating), which is made of lotrafilcon A, has an averagedcoefficient of friction of about 1.8. A contact lens having an LbL orantimicrobial coating has a smaller averaged COF (Table 3). TABLE 3 LbLor Antimicrobial Coating on a Contact lens (lotrafilcon A) COFPAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA 1.32 ± 0.12¹PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-6 1.29 ± 0.11¹PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-6/ 1.11 ± 0.13¹ PAAPAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-10 1.41 ± 0.02²PAA/Q6-6/PAA/Q6-6/PAA/Q6-6/PAA/Q6-6/PAA 1.31 ± 0.03²

[0156] It has been found that the desirable bulk properties of the lens,such as oxygen permeability, ion permeability, and optical propertiesare not significantly affected by the antimicrobial coating comprisingone or more layer of polyquat (PQ6-6, PQ6-10 or PQ6-12) on the lens. Theion permeability of a contact lens measures the ability of ions todiffuse through the contact lens. The Dk value of a contact lens isgenerally a measure of the ability of a gas, such as oxygen, to diffusethrough a contact lens. A more detailed description of the ionpermeability and Dk value can be obtained by reference to U.S. Pat. No.5,760,100.

EXAMPLE 7

[0157] The potency of polyquat against Pseudomonas aeruginosa GSU #3 istested at a concentration of 0.5, 1, 5 and 10 ppm. The inoculum isbetween 5×10⁵-1×10⁶ cfu/ml. There is more than 3-log reductiondemonstrated by the biocidal assay. Minimum inhibition concentrations(MICs) are determined and shown in Table 4.

[0158] Cytotoxicity of polyquat is also evaluated according to the USPElution Test (“Biological Reactivity Tests, In-Vitro: Elution Test”, TheUnited States Pharmacopeial Convention, Inc.). Cell cultures, L929mammalian fibroblasts (ATCC cell line CCL1, NCTC clone 929), are grownto a near confluent monolayer in 6 well plates (individual wells are 35mm diameter). A polyquat solution is diluted with serum-supplementedcell culture medium at 25% test solution concentration. Theserum-supplemented cell culture medium is prepared by mixing 1000 mLEagle's sterile minimum essential medium (MEM), 100 mL serum, 10 mlL-glutamine solution and antibiotic-antimycotic solution. Each cultureis examined microscopically after 48 hours using trypan blue for thepresence of morphological changes, reduction in cell density or celllysis induced by the polyquat solution. The results of cytotoxicityassay are shown in Table 4. TABLE 4 Polyquat Potency (MIC) CytotoxicityPQ6-6 2-10 ppm Passed at 50 ppm PQ6-10 0.5 ppm Passed at 25 ppm PQ6-120.5 ppm Failed at 25 ppm

[0159] Contact lenses (made of lotrafilcon A, having an LbL coating ofPAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA and contact lenses (lotrafilcon A)having an antimicrobial coating ofPAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-10 are evaluated forcytotoxicity according to the L929 Cell Growth Assay (Coulter CounterMethod). For this assay, cells grown under controlled conditions aremonitored for their ability to survive and grow following initialexposure and incubation with extracts of lenses. The lenses are rinsedwith 10 mL of 0.9% Sodium Chloride Injection, USP, and then extractedusing 20 lenses in 10 mL of 0.9% Sodium Chloride Injection, USP, at121±2° C. for 1 hour. The extract is diluted with growth media(serum-supplemented MEM) to 50% extract concentration and is applied tothe L929 cells. Cell counts are determined upon initiation of the test(Initial, Time=0) and after 72 hours with and without addition of testsample (lens extract). The calculation of the percent inhibition of cellgrowth induced by the extract is determined by comparison of cell growthfor the control cultures to the test cultures. This test evaluated theability of cells to survive a toxic insult as measured by retention ofproliferative ability. Results are shown in Table 5. TABLE 5 Tests andControl Sample description % inhibition Test Samples: Contact lenses(lotrafilcon A) with LbL coatings 12 Contact lenses (lotrafilcon A) withantimicrobial coatings 10 Control Samples: Sodium Chloride Injection(0.9% NaCl) (negative control) 0 5% ethanol solution (w/PBS) (positivecontrol) 100

[0160] The results in Table 5 indicate that there is no significantdifference between contact 20 lenses having LbL coatings and contactlenses having antimicrobial coatings. Both types of contact lenses canbe considered non-cytotoxic since the growth inhibition is less than30%, which is the threshold for a cytotoxic response in the eye.

EXAMPLE 8

[0161] In vivo Toxicity Tests

[0162] In vivo toxicity of antimicrobial coatings on contact lenses istested by trying these contact lenses with antimicrobial coatings on theeyes of New Zealand white rabbits. Contact lenses, designed toaccommodate rabbit eyes and made of lotrafilcon A, were manufactured. Anantimicrobial coating comprising 4½ bilayer(PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA) and a capping layer of PQ6-12 isapplied onto each lens in accordance with the procedure described inExample 2. The eyes of New Zealand white rabbits are examined after theywear the contact lenses with the antimicrobial coatings on eye for 7days and 6 nights. Microscopic evaluation of the ocular tissue sectionsreveals no evidence of corneal or conjunctival damage in any of the testor control eyes.

[0163] Intra-Stromal Corneal Implantation Test

[0164] Control lenses (made of lotrafilcon A and with an LbL coatingcomprising 4½ bilayer, PAA/PAH/PAA/PAH/PA/PAH/PAA/PAH/PAA), and segmentsof contact lenses with antimicrobial coatings each comprising a cappinglayer of PQ6-12 and 4½ bilayer (PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA) aresurgically implanted into corneal stroma of New Zealand white rabbits toevaluate toxicity reactions. The lenses are inserted into the eye tomid-depth in the corneal stroma. All eyes are harvested forhistopathology after one week of wear. There are no signs ofinflammation.

[0165] Intramuscular Implantation Test

[0166] New Zealand white rabbits are implanted with strips of theantimicrobial contact lenses and the control lenses on the dorsal sidefor a period of seven days. The animals are observed daily to insureproper healing of the implant sites and for clinical sites of toxicity.The implanted sites are excised from the rabbits and examined withmacroscopic observations and histopathology analysis. None of the testanimals exhibits signs of toxicity over the course of the study.Microscopic evaluation of the test article sites indicates no signs ofinflammation, fibrosis, hemorrhage, necrosis of degeneration as comparedto the negative or to the predicate control article sites.

[0167] All results shown in the above examples demonstrate that theantimicrobial coatings on contact lenses have a high antimicrobialefficacy, a low toxicity, low coefficient of friction (with an averagedvalue of less than 1.4), and increased hydrophilicity (characterized byan averaged contact angle of less than 80 degree) while maintaining thedesired bulk properties such as oxygen permeability and ion permeabilityof lens material. Such lenses are useful as extended-wear contactlenses.

[0168] Although various embodiments of the invention have been describedusing specific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. It is to be understood that changes andvariations may be made by those skilled in the art without departingfrom the spirit or scope of the present invention, which is set forth inthe following claims. In addition, it should be understood that aspectsof the various embodiments may be interchanged either in whole or inpart. Therefore, the spirit and scope of the appended claims should notbe limited to the description of the preferred versions containedtherein.

What is claimed is:
 1. A medical device, comprising a core material andan antimicrobial surface coating, wherein said medical device havingsaid antimicrobial surface coating thereon has the following surfaceproperties: (a) a low coefficient of friction with a averaged value ofless than 1.55, preferably less than 1.45, more preferably less than1.4, most preferably less than 1.35, and (b) an adequate hydrophilicitywhich is characterized by having an averaged contact angle of less than80 degree.
 2. A medical device of claim 1, wherein said antimicrobialcoating comprises at least an antimicrobial agent.
 3. A medical deviceof claim 2, wherein the antimicrobial agent is selected from the groupconsisting of antibiotics, lactoferrin, metal chelating agents,substituted and unsubstituted polyhydric phenols, amino phenols,alcohols, acid and amine derivatives, and quaternary ammoniumgroup-containing compounds.
 4. A medical device of claim 1, wherein saidantimicrobial surface coating comprises polymeric quaternary ammoniumgroup-containing compound (polyquats).
 5. A medical device of claim 4,wherein said antimicrobial surface coating comprises one or more layersof polyquat of formula (I) or (II).

wherein R₁, R₂, R₃ and R₄, independently of one another, are C₁-C₁₀hydrocarbon radicals, preferably C₁ to C₆ alkyl radicals or C₁ to C₆alkyl radicals having one or more hydroxyl groups, more preferablymethyl, ethyl, or benzyl radicals, even more preferably methyl radicals,wherein A and B, independently of one another, are n-alkylene groupshaving 3 to 15 carbon atoms or n-alkylene groups having 3 to 15 carbonatoms and one or more hydroxyl groups, wherein the index y is a numberfrom about 10 to 500, preferably a number from 25 to 400, and morepreferably a number from 50 to 300, wherein X is chlorine, bromine, oriodine, wherein the index n is a number from about 100 to 5000,preferably a number from 500 to 4000, and more preferably a number from500 to 3000, wherein R₅ and R₆, independently of one another, aren-alkyl groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to10 carbon atoms and one or more hydroxyl groups.
 6. A medical device ofclaim 5, wherein said antimicrobial surface coating comprises one ormore layers of polyquat of formula (I) in which one of A and B ishexamethylene radical (—CH₂CH₂CH₂CH₂CH₂CH₂—) and the respective otherone is an n-alkylene group having 6 to 12 carbon atoms.
 7. A medicaldevice of claim 5, wherein the medical device is an ophthalmic lens. 8.An ophthalmic lens of claim 7, wherein the ophthalmic lens is a contactlens.
 9. A contact lens of claim 8, wherein the layers of polyquat arecovalently coupled to the core material via coupling agents.
 10. Acontact lens of claim 8, wherein the antimicrobial surface coating is anLbL coating.
 11. A contact lens of claim 10, wherein the antimicrobialsurface coating comprises a capping layer of the polyquat of formula (I)or (II).
 12. A contact lens of claim 10, wherein the antimicrobialsurface coating comprises at least one polyanionic-polyquat bilayerwhich is composed of one layer of a polyanionic material and one layerof the polyquat of formula (I) or formula (II).
 13. A contact lens ofclaim 12, wherein the polyanionic material is selected from the groupconsisting of polyacrylic acid, polymethacrylic acid,poly(thiophen-3-acetic acid), poly(4-styrenesulfonic acid), derivativesthereof and mixtures thereof.
 14. A contact lens of claim 12, whereinthe antimicrobial surface coating further comprises at least onepolyelectrolyte bilayer which is composed of one layer of thepolyanionic material and one layer of a polycationic material.
 15. Acontact lens of claim 14, wherein the polycationic material is selectedfrom the group consisting of poly(allylamine hydrochloride),poly(ethyleneimine), poly(vynylbenzyltriamethylamine), polyaniline,polypyrrole, poly(pyridinium acetylene), derivatives thereof andmixtures thereof, wherein the polyanionic material is selected from thegroup consisting of polyacrylic acid, polymethacrylic acid,poly(thiophen-3-acetic acid), poly(4-styrenesulfonic acid), derivativesthereof and mixtures thereof.
 16. A contact lens of claim 8, whereinsaid core material is a hydrogel.
 17. A contact lens of claim 16,wherein said hydrogel is a siloxane-containing polymer.
 18. A method forproducing a medical device having an antimicrobial coating, comprisingthe steps of: (a) functionalizing the surface of the medical device; and(b) covalently coupling polyquats of formula (I) or (II) to thefunctionalized surface of the medical device to form the antimicrobialcoating on the medical device.
 19. A method of claim 18, wherein saidmedical device is an ophthalmic device.
 20. A method of claim 19,wherein said ophthalmic lens is a contact lens.
 21. A method of claim20, wherein the contact lens is functionalized with a diazirinecompound.
 22. A method for producing a medical device having a corematerial and an antimicrobial coating, comprising applying at least onelayer of polyquats of formula (I) or (II) onto the medical device

wherein R₁, R₂, R₃ and R₄, independently of one another, are C₁-C₁₀hydrocarbon radicals, preferably C₁ to C₆ alkyl radicals or C₁ to C₆alkyl radicals having one or more hydroxyl groups, more preferablymethyl, ethyl, or benzyl radicals, even more preferably methyl radicals,wherein A and B, independently of one another, are n-alkylene groupshaving 3 to 15 carbon atoms or n-alkylene groups having 3 to 15 carbonatoms and one or more hydroxyl groups, wherein the index y is a numberfrom about 10 to 500, preferably a number from 25 to 400, and morepreferably a number from 50 to 300, wherein X is chlorine, bromine, oriodine, wherein the index n is a number from about 100 to 5000,preferably a number from 500 to 4000, and more preferably a number from500 to 3000, wherein R₅ and R₆, independently of one another, aren-alkyl groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to10 carbon atoms and one or more hydroxyl groups.
 23. A method of claim22, comprising applying at least one layer of polyquats of formula (I)in which one of A and B is hexamethylene radical (—CH₂CH₂CH₂CH₂CH₂CH₂—)and the respective other one is an n-alkylene group having 6 to 12carbon atoms.
 24. A method of claim 22, wherein the layer of polyquatsis applied onto the medical device by immersing said medical device in afirst solution of polyquat of formula (I) or (II) or by spraying asecond solution of polyquat of formula (I) or (II) onto the surface ofsaid medical device.
 25. A method of claim 24, further comprisingapplying at least one layer of polyanionic materials.
 26. A method ofclaim 25, wherein the layer of polyanionic materials is applied onto themedical device by immersing said medical device in a first solution ofpolyanionic materials or by spraying a second solution of polyanionicmaterials onto the surface of said medical device.
 27. A method of claim26, further comprising the steps of: (a) contacting the core materialwith a solution of the first polyionic material to form a layer of thefirst polyionic material; (b) optionally rinsing said medical device bycontacting said medical device with a rinsing solution; (c) contactingsaid medical device with a solution of a second polyionic material to alayer of the second polyionic material on top of the layer of the firstpolyionic material, wherein said second polyionic material has chargesopposite of the charges of the first polyionic material; and (d)optionally rinsing said medical device by contacting said lens with therinsing solution.
 28. A method of claim 27, wherein at least one of saidcontacting occurs by immersion said medical device in a solution.
 29. Amethod of claim 27, wherein at least one of said contacting occurs byspraying a solution onto the medical device.
 30. A method of claim 27,wherein said method comprises repeating steps (a) through (D between 3to 20 times.
 31. A method of claim 26, wherein said method comprisesdipping said medical device in a solution containing a polyanionicmaterial and polycationic material in an amount such that the molarcharge ratio of said solution is from about 3:1 to about 100:1.
 32. Amethod of claim 31, wherein said molar charge ratio of said solution is10:1.
 33. A method for producing a contact lens having an antimicrobialcoating, comprising the steps of: (a) forming a mold for making thecontact lens, wherein the mold comprises a first mold portion defining afirst optical surface and a second mold portion defining a secondoptical surface, wherein said first mold portion and said second moldportion are configured to receive each other such that a contactlens-forming cavity is formed between said first optical surface andsaid second optical surface; (b) applying a transferable antimicrobialcoating, using a layer-by-layer polyelectrolyte deposition technique,onto at least one of said optical surface, wherein the transferableantimicrobial coating comprises at least one layer of polyquat offormula (I) or (II)

 wherein R₁, R₂, R₃ and R₄, independently of one another, are C₁-C₁₀hydrocarbon radicals, preferably C₁ to C₆ alkyl radicals or C₁ to C₆alkyl radicals having one or more hydroxyl groups, more preferablymethyl, ethyl, or benzyl radicals, even more preferably methyl radicals,wherein A and B, independently of one another, are n-alkylene groupshaving 3 to 15 carbon atoms or n-alkylene groups having 3 to 15 carbonatoms and one or more hydroxyl groups, wherein the index y is a numberfrom about 10 to 500, preferably a number from 25 to 400, and morepreferably a number from 50 to 300, wherein X is chlorine, bromine, oriodine, wherein the index n is a number from about 100 to 5000,preferably a number from 500 to 4000, and more preferably a number from500 to 3000, wherein R₅ and R₆, independently of one another, aren-alkyl groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to10 carbon atoms and one or more hydroxyl groups; (c) positioning saidfirst mold portion and said second mold portion such that said moldportions receive each other and said optical surfaces define saidcontact lens forming cavity; (d) dispensing a polymerizable compositioninto said contact lens-forming cavity; (e) curing said polymerizablecomposition within said contact lens-forming cavity such that thecontact lens is formed, whereby at least a portion of said transferablecoating detaches from said at least one optical surface of said moldportion and reattaches to said formed contact lens such that saidcontact lens becomes coated with the antimicrobial coating.
 34. A methodof claim 32, wherein said transferable antimicrobial coating is appliedonto at least one of said optical surfaces by immersing said mold in afirst solution of polyquat of formula (I) or (II) or by spraying asecond solution of polyquat of formula (I) or (II) onto at least one ofsaid optical surfaces.
 35. A method for characterizing coefficient offriction of a contact lens, comprising the steps of: (a) sliding saidcontact lens, at a prescribed speed, against a biologically relevantsubstrate under a load of weight; (b) measuring simultaneously thenormal (N) and frictional (F_(T)) forces that are produced from theinteraction between said contact lens and the biologically relevantsubstrate lubricated with a lubricant under said load of weight; and (c)calculating the coefficient of friction (μ) of the contact lens based onthe equation of μ=F _(T) /N
 36. A method of claim 35, wherein said loadof weight is from about 1 gram to about 10 gram, preferably from about 1gram to about 5 gram, more preferably from about 2 grams to from 4grams.
 37. A method of claim 35, wherein said biologically relevantsubstrate is a powder-free surgical glove with Biogel® Coating″ fromRegent®.
 38. A method of claim 35, wherein said lubricant is water,saline or artificial tear fluid.
 39. An apparatus for characterizingcoefficient of friction of a contact lens, comprising: (a) ahorizontally movable platform that is capable of moving uniaxially atvarious speeds and accelerations; (b) a biologically relevant substratewhich is mounted onto said horizontally movable table platform; (c) astationary lens holder assembly for holding said contact lens and forplacing said contact lens in contact with said biologically relevantsubstrate; and (d) a plurality of force measuring means forsimultaneously measuring normal force and tangential force when saidcontact lens slides against said biologically relevant substrate,wherein the normal and tangential forces are produced from theinteraction between said contact lens and said biologically relevantsubstrate lubricated with a lubricant under a load of weight, whereinthe load of weight is applied to said contact lens in normal directionto said contact lens.
 40. An apparatus of claim 39, wherein the loadweight is from about 1 gram to about 10 gram, preferably from about 1gram to about 5 gram, more preferably from about 2 grams to from 4grams.
 41. An apparatus of claim 39, comprising three force-measuringmeans: a first force measuring means, a second force-measuring means anda third force-measuring means.
 42. An apparatus of claim 41, wherein thefirst force-measuring means is attached to the lens holder assembly tomeasure tangential forces, wherein the second and the thirdforce-measuring means reside under the horizontally movable platform tomeasure normal forces in the downward direction.
 43. An Apparatus ofclaim 39, wherein said stationary lens holder assembly comprises aholder bracket and a lens holder having a lens-supporting surface,wherein the lens-supporting surface has a convex curvature capable ofaccommodating the back (concave) surface of a contact lens, wherein thelens holder is held by a means in the center of the holder bracket. 44.An apparatus of claim 43, wherein said holder bracket has ageometrically symmetrical shape.
 45. An apparatus of claim 44, whereinthe geometrically symmetrical shape is selected from the groupconsisting of circle, oval, diamond, triangle, square, rectangular,letter A-shape, and letter U-shape.
 46. An apparatus of claim 45,wherein the geometrically symmetrical shape is letter A-shape ortriangle.